John C Stendahl1, Zhao Liu2, Nabil E Boutagy1, Eliahoo Nataneli3, Farhad Daghighian3, Albert J Sinusas4,5,6. 1. Section of Cardiovascular Medicine, Department of Medicine, Yale Translational Research Imaging Center, Yale University School of Medicine, New Haven, CT, 06520, USA. 2. Department of Biomedical Engineering, Yale University, School of Engineering and Applied Science, New Haven, CT, 06520, USA. 3. IntraMedical Imaging, LLC, 12569 Crenshaw Blvd, Hawthorne, CA, 90250, USA. 4. Section of Cardiovascular Medicine, Department of Medicine, Yale Translational Research Imaging Center, Yale University School of Medicine, New Haven, CT, 06520, USA. albert.sinusas@yale.edu. 5. Department of Radiology and Biomedical Imaging, Yale University School of Medicine, P.O. Box 208017, Dana 3, New Haven, CT, 06520-8017, USA. albert.sinusas@yale.edu. 6. Department of Biomedical Engineering, Yale University, School of Engineering and Applied Science, New Haven, CT, 06520, USA. albert.sinusas@yale.edu.
Abstract
BACKGROUND: We have set out to develop a catheter-based theranostic system that: (a) identifies diseased and at-risk myocardium via endocardial detection of systemically delivered β-emitting radiotracers and (b) utilizes molecular signals to guide delivery of therapeutics to appropriate tissue via direct intramyocardial injection. METHODS: Our prototype device consists of a miniature β-radiation detector contained within the tip of a flexible intravascular catheter. The catheter can be adapted to incorporate an injection port and retractable needle for therapeutic delivery. The performance of the β-detection catheter was assessed in vitro with various β-emitting radionuclides and ex vivo in hearts of pigs following systemic injection of 18F-fluorodeoxyglucose (18F-FDG) at 1-week post-myocardial infarction. Regional catheter-based endocardial measurements of 18F activity were compared to regional tissue activity from PET/CT images and gamma counting. RESULTS: The β-detection catheter demonstrated sensitive in vitro detection of β-radiation from 22Na (β+), 18F (β+), and 204Tl (β-), with minimal sensitivity to γ-radiation. For 18F, the catheter demonstrated a sensitivity of 4067 counts/s/μCi in contact and a spatial resolution of 1.1 mm FWHM. Ex vivo measurements of endocardial 18F activity with the β-detection catheter in the chronic pig infarct model demonstrated good qualitative and quantitative correlation with regional tissue activity from PET/CT images and gamma counting. CONCLUSION: The prototype β-detection catheter demonstrates sensitive and selective detection of β- and β+ emissions over a wide range of energies and enables high-fidelity ex vivo characterization of endocardial activity from systemically delivered 18F-FDG.
BACKGROUND: We have set out to develop a catheter-based theranostic system that: (a) identifies diseased and at-risk myocardium via endocardial detection of systemically delivered β-emitting radiotracers and (b) utilizes molecular signals to guide delivery of therapeutics to appropriate tissue via direct intramyocardial injection. METHODS: Our prototype device consists of a miniature β-radiation detector contained within the tip of a flexible intravascular catheter. The catheter can be adapted to incorporate an injection port and retractable needle for therapeutic delivery. The performance of the β-detection catheter was assessed in vitro with various β-emitting radionuclides and ex vivo in hearts of pigs following systemic injection of 18F-fluorodeoxyglucose (18F-FDG) at 1-week post-myocardial infarction. Regional catheter-based endocardial measurements of 18F activity were compared to regional tissue activity from PET/CT images and gamma counting. RESULTS: The β-detection catheter demonstrated sensitive in vitro detection of β-radiation from 22Na (β+), 18F (β+), and 204Tl (β-), with minimal sensitivity to γ-radiation. For 18F, the catheter demonstrated a sensitivity of 4067 counts/s/μCi in contact and a spatial resolution of 1.1 mm FWHM. Ex vivo measurements of endocardial 18F activity with the β-detection catheter in the chronic pig infarct model demonstrated good qualitative and quantitative correlation with regional tissue activity from PET/CT images and gamma counting. CONCLUSION: The prototype β-detection catheter demonstrates sensitive and selective detection of β- and β+ emissions over a wide range of energies and enables high-fidelity ex vivo characterization of endocardial activity from systemically delivered 18F-FDG.
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